[Paclitaxel (Taxol) and docetaxel (Taxotere): results of phase II trials in monochemotherapy]. / Paclitaxel (Taxol) et docetaxel (Taxotère): résultats des essais de phase II en monochimiothérapie.

The taxanes, paclitaxel and docetaxel, are the two presents clinically available representatives of a cytotoxic class with a new mechanism of action: they enhance microtubule assembly and inhibit their depolymerization. Their activity has been demonstrated in ovarian, breast and lung cancers. Paclitaxel and docetaxel are also promising agents in the treatment of head and neck, gastric and pancreatic cancer. Neutropenia is the dose limiting toxicity. Currently, use of premedication allows to circumvent hypersensitivity reactions encountered earlier with paclitaxel. For docetaxel, measures to prevent fluid retention are essential.

Over-expression of the S13 ribosomal protein in actively growing cells.

In order to define biological markers of aggressiveness, 2 rat colon-carcinoma cell lines differing by their tumorigenicity were used to clone genes over-expressed in colon carcinoma as compared with normal epithelial cells. A progressive rat colon-carcinoma clone (PROb) cDNA library was hybridized with 32P-cDNA synthesized from mRNA prepared from these PROb cells, or from regressive cells (REGb) derived from the same tumor. Several clones were isolated after the initial screening. The specificity of each clone was confirmed by RNA blotting. One of these (B9) was found to hybridize to an mRNA 30-fold more abundant in PROb cells than in normal adult rat colon, and was therefore selected for further study. No gene amplification was detected by Southern blot analysis, indicating that the difference in mRNA content was most likely due to an increased transcription of this gene. Sequencing of the cDNA revealed approximately 98% homology with the rat S13 ribosomal protein. The expression level of this gene was determined in a series of rat cell lines with different growth rates. A good correlation was found between these 2 parameters. Our data suggest that the S13 ribosomal-protein gene can be used to evaluate the growth rate of tumor cells, which might be correlated with their aggressiveness. In an initial trial experiment, S13 ribosomal-protein mRNA was detected in a series of human colorectal tumors by in situ hybridization. A strong signal was seen in the 4 tumors analyzed.

High-fold expansion of human cytotoxic T-lymphocytes specific for autologous melanoma cells for use in immunotherapy.

We set up a culture protocol that consistently allows high-fold expansion of tumor-specific T-lymphocytes from most melanoma-invaded biopsies with low doses of recombinant interleukin-2 (rIL-2). Between 2-60 x 10(6) T-lymphocytes could be obtained and cryopreserved from 12 out of 13 patients, by culturing only 50 mm3 tumor tissue with rIL-2. Thawed lymphocytes from 11 of these patients could then be expanded by a median factor of 32,800 by culturing them successively in microplates on irradiated feeder cells with rIL-2 for approximately 2 weeks and then in culture bags or flasks with only rIL-2 for 1-2 additional weeks. Dead feeder cells disappeared during the last phase of the lymphocyte culture with rIL-2. Interestingly, each time they were expanded under these conditions, tumor-infiltrating lymphocytes (TIL) or lymph-node lymphocytes developed a lytic activity apparently restricted to the autologous melanoma line. Tumor-specific lysis, which was maximum at around the end of T-lymphocyte expansion, ranged between 31-63% lysis at an effector:target (E:T) ratio of 20:1. This culture method would thus appear to be suitable for reliable production of over 10(10) T-lymphocytes with good tumor-specific lytic activity from most melanoma-invaded biopsy. It should permit analysis of the immunotherapeutic potential of these populations reinjected into cancer patients.